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Archive - Oct 25, 2011

Protein Panel Predicts Mortality in Idiopathic Pulmonary Fibrosis

A panel of blood proteins can predict which patients with the progressive lung disease idiopathic pulmonary fibrosis (IPF) are likely to live at least five years or to die within two years, say researchers at the University of Pittsburgh School of Medicine and Centocor R&D. The findings, published online on October 20, 2011 in the American Journal of Respiratory and Critical Care Medicine, could help doctors determine those patients in imminent need of a lung transplant and those who can wait a while longer. Fifty percent of IPF patients die within three years of diagnosis, but others will do well for long periods of time, explained investigator Dr. Naftali Kaminski, professor of medicine, pathology, human genetics, and computational biology, Pitt School of Medicine, and director, The Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease at the University of Pittsburgh Medical Center (UPMC). In the disease, breathing becomes increasingly impaired as the lungs progressively scar. "It's hard to tell based on symptoms alone which patients are in the greatest danger," Dr. Kaminski said. "This biomarker panel has predictive power that can guide our treatment plan. It may also help us design more effective research trials because we'll be able to better match experimental therapies with the most appropriate patients." The research team collected blood samples from 241 IPF patients. They measured the levels of 92 candidate proteins in 140 patients and found that high concentrations of five particular proteins that are produced by the breakdown of lung tissue predicted poor survival, poor transplant-free survival, and poor progression-free survival regardless of age, sex, and baseline pulmonary function. They then confirmed the results in a second group of 101 patients.

Junk DNA May Underlie Major Differences Between Humans and Chimps

For years, scientists believed the vast phenotypic differences between humans and chimpanzees would be easily explained – the two species must have significantly different genetic makeups. However, when their genomes were later sequenced, researchers were surprised to learn that the DNA sequences of human and chimpanzee genes are nearly identical. What then is responsible for the many morphological and behavioral differences between the two species? Researchers at the Georgia Institute of Technology (Georgia Tech) have now determined that the insertion and deletion of large pieces of DNA near genes are highly variable between humans and chimpanzees and may account for major differences between the two species. The research team led by Georgia Tech Professor of Biology John McDonald has verified that while the DNA sequence of genes between humans and chimpanzees is nearly identical, there are large genomic “gaps” in areas adjacent to genes that can affect the extent to which genes are “turned on” and “turned off.” The research shows that these genomic “gaps” between the two species are predominantly due to the insertion or deletion (INDEL) of viral-like sequences called retrotransposons that are known to comprise about half of the genomes of both species. The findings were published October 25, 2011, in the online, open-access journal Mobile DNA. “These genetic gaps have primarily been caused by the activity of retroviral-like transposable element sequences,” said Dr. McDonald. “Transposable elements were once considered ‘junk DNA’ with little or no function. Now it appears that they may be one of the major reasons why we are so different from chimpanzees.” Dr.

Transcription Factor SP4 Found Reduced in Bipolar Disorder

Low levels of a brain protein that regulates gene expression may play a role in the origin of bipolar disorder, a complex and sometimes disabling psychiatric disease. As reported in the August-September 2011 issue of Bipolar Disorders, the journal of The International Society for Bipolar Disorders, levels of SP4 (specificity protein 4) were lower in two specific regions of the brain in postmortem samples from patients with bipolar disorder. The study suggests that normalization of SP4 levels could be a relevant pharmacological strategy for the treatment of mood disorders. "We found that levels of SP4 protein in the brain's prefrontal cortex and the cerebellum were lower in postmortem samples from patients with bipolar disorder, compared with samples from control subjects who did not have the disease," said co-senior author Dr. Grace Gill, an associate professor in the department of anatomy and cellular biology at Tufts University School of Medicine and a member of the neuroscience; genetics; and cell, molecular and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts. Dr. Gill's laboratory team at Tufts collaborated with researchers from Spain and used postmortem samples from Spain's University of the Basque Country brain collection program to examine SP4 protein levels in samples from 10 bipolar subjects and 10 control subjects matched for gender, age, and time since death. The team focused on the prefrontal cortex and the cerebellum because brain imaging studies suggest that bipolar disorder is associated with changes in the structure of these brain regions. Little is known about the cellular and molecular changes that occur in bipolar disorder, especially in the cerebellum.